tbuckley/cabot-search huggingface dataset:
Abstract 13149: Mental Stress-Induced Hemodynamic Changes and Cardiovascular Outcomes
Authors: Brian Cheung, Zakaria Almuwaqqat, Jeong Hwan Kim, Muhammad Hammadah, Amit J Shah, Yi-An Ko, lisa elon, Samaah Sullivan, Anish Shah, Ayman Alkhoder, Bruno B Lima, Brad Pearce, Laura Ward, Michael Kutner, Yingtian Hu, Tene T Lewis, Ernest V Garcia, Jonathon A Nye, David Sheps, Paolo Raggi, James Douglas Bremner, Viola Vaccarino, Arshed A Quyyumi
Journal: Circulation (2022)

Introduction: Hemodynamic responses to mental stress (MS) have been associated with adverse CV outcomes. We investigated if hemodynamic responses during laboratory MS testing are predictive of outcomes. Hypothesis: Lower rate pressure product (RPP) changes during MS testing are predictive of adverse CV events. Methods: Patients recruited into the Mental Stress Ischemia Prognosis Study and Myocardial Infarction and Mental Stress Study 2 studies underwent MS testing with a standardized public speaking stressor and followed for incident CV death, MI rates (primary endpoint) and heart failure hospitalizations (secondary endpoint). Maximum changes in the RPP during MS were calculated. A generalized linear mixed model determined predictors of RPP change, and Prentice, Williams, Peterson model gap time approach was used for analysis of recurrent events after adjustment for demographic and clinical variables. Results: In 919 patients (mean 59.6 years; 65.6% men), the median change in RPP was 5,112 mmHg x beats/minute (IQR, 3,666 - 7,120). Patients with lower RPP changes (&lt;median) during MS were more likely to have a lower resting RPP, be male, and have a history of smoking, obesity, and heart failure. Serum epinephrine levels (22.5 ± 37.3 pg/mL; p&lt;0.001) increased after MS and correlated with RPP changes (r = 0.32; p &lt; 0.001). During a mean follow-up of 4.6 years, there were 135 CV death and MI events (3.2/100 patient-years) and 279 events including HF hospitalizations (6.7 events/100 patient-years). After adjusting for the baseline RPP, demographics, clinical factors, and medication, patients with lower change in RPP during MS had higher primary [HR, 1.7 (95% CI, 1.1 - 2.5); p = 0.009] and secondary events [HR, 1.5 (95% CI, 1.1 - 2.0); p = 0.006]. Conclusions: A reduced change in RPP during MS is independently associated with worse outcomes in patients with CAD. Whether hemodynamic reactivity during MS can be clinically used to identify residual risk needs further evaluation.
Abstract 12829: Biomimetic Cardiac Tissue Culture Model to Emulate Cardiac Physiology and Pathophysiology <i>Ex Vivo</i>
Authors: Jessica Miller, Moustafa H Meki, Ahmed Elnakib, Qinghui Ou, Riham Abouleisa, Abou Bakr M Salama, Ahmad Gebreil, Cindy Lin, Hisham Abdeltawab, Fahmi Khalifa, Bradford G Hill, Najah Abi Gerges, Roberto Bolli, Ayman El-Baz, Guruprasad Giridharan, Tamer Mohamed
Journal: Circulation (2022)

Introduction: There is an urgent need for a reliable in vitro system to accurately replicate the cardiac physiological and pathological environment for drug testing. The limited availability of human heart tissue culture systems has led to inaccurate interpretations of cardiac-related drug effects. Our group developed a culture system for pig/human heart slices that enables functional and structural viability for 6 days using continuous electrical stimulation and enriched media. This culture system can more reliably detect cardiotoxic effects compared to hiPSC-CMs. However, by day 10, the slices undergo cardiomyocyte dedifferentiation and fibrotic remodeling making them inadequate for long-term drug testing. Hypothesis: To determine whether incorporating physiological mechanical, and humoral cues within the culture system can fully emulate cardiac physiology and pathophysiology in culture. Methods and results: We have developed a novel c ardiac t issue c ulture m odel (CTCM) that can electro-mechanically stimulate heart slices with physiological (0 to 80 mmHg) preload and afterload during each cardiac cycle. After 12 days in culture, this approach alone partially improved the viability of heart slices but did not maintain the structural integrity. Therefore, following a small molecule screening, we found that incorporating 100 nM tri-iodothyronine (T3) and 1 μM dexamethasone (Dex) into our culture media preserved the structural integrity of the slices for 12 days. When combined with T3/Dex, the CTCM system fully maintained the transcriptional profile, viability, metabolic activity, and structural integrity for 12 days at the same levels as fresh heart tissue. Furthermore, to test the ability of the CTCM to emulate cardiac hypertrophy, increasing the peak pressure to 140 mmHg resulted in induced cardiac hypertrophy within 6 days in culture as indicated by a 3-fold increase in NT-ProBNP release, increased NFATC4 and P-ERK expression, and increased cardiomyocyte cross-sectional area. Conclusions: This new CTCM heart slice culture system incorporating physiological electromechanical and humoral cues can emulate cardiac physiology and pathophysiology in culture, which could be used for drug screening for new therapeutics and cardiotoxins.
Abstract 13308: Complementary Investigations of Plasma Proteomics Identify Novel Protein Associations With Incident Diabetes and Glucose Metabolism
Authors: Michael Y Mi, Helene T Cronje, Thomas R Austin, Mary L Biggs, David S Siscovick, Rozenn N Lemaitre, Bruce M Psaty, Russell P Tracy, Luc Djousse, Jorge R Kizer, Joachim H IX, Nona Sotoodehnia, Prashant Rao, Jeremy M Robbins, Jacob L Barber, Mark A Sarzynski, Clary Clish, Claude Bouchard, Ken J Mukamal, Majken K Jensen, Robert E Gerszten
Journal: Circulation (2022)

Introduction: Type 2 diabetes (T2D) is a cardiovascular disease risk equivalent and likely results from broad metabolic changes, which high throughput proteomics have helped to unravel. Prior studies are limited by proteomic coverage, cross sectional design, and lack of physiologic phenotyping. Hypothesis: Complementary proteomic studies of incident T2D and physiologic responses to an intravenous glucose tolerance test (IVGTT) will identify novel proteins with roles in glucose homeostasis and future risk of T2D. Methods: Cardiovascular Health Study (CHS) and HERITAGE study participants without diabetes underwent SomaScan ® profiling of 4,776 plasma proteins. HERITAGE participants underwent IVGTT, from which insulin sensitivity index (S I ), acute insulin response to glucose (AIR G ), and glucose effectiveness (S G ) were derived. We used Cox regression to test protein associations with 18-year incident T2D in CHS, and multivariable linear regression to test protein associations with IVGTT measures in HERITAGE. Results: In CHS (N = 2631, 74 ± 5 years, 62% female, 14% Black), 57 proteins were significantly associated with incident T2D after comprehensive covariate and multiple testing adjustment. Of these, 44, 9, and 8 were associated with S I , AIR G , and S G respectively in HERITAGE (N = 752, 35 ± 14 years, 55% female, 38% Black) (Figure). Notable findings include beta-glucuronidase, which associated with increased T2D risk (HR 1.46 per SD increase in log 2 protein level) and lower S G , suggesting a role in insulin-independent glucose disposal, and thrombospondin-2, which associated with increased T2D risk (HR 1.26 per SD), lower AIR G , and not with S I , indicating that it may be a marker of pancreatic dysfunction. Conclusions: By integrating proteomics from two complementary prospective cohorts using different but related outcomes, we identified 34 novel protein-T2D associations, and characterized their relationship with physiologic axes of glucose metabolism.
Abstract 13037: RAS Inhibition is Associated With Higher Risk of 60-Day COVID-19-Induced Myocarditis
Authors: ALI VAELI ZADEH, Alan Wong, Ashvin Zachariah, Elias Collado, Joshua Larned
Journal: Circulation (2022)

Background: COVID-19 related myocarditis (MC) can manifest with no symptoms, chest pain, life-threatening arrhythmia with hemodynamic instability, or new heart failure. Evidence suggests that RAS inhibition may be beneficial for some patients during COVID-19 infection; however, the effect of these drugs on risk of developing COVID-19-induced MC is not well characterized. Methods: Using ICD-10 codes, a cohort of patients admitted between March-October 2020 with the primary diagnosis of COVID-19 was identified from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). Use of RAS inhibitors over the past 6 months was used to split the cohort into two case-control matched groups based on age, gender, and Elixhauser Comorbidity Index. Using the same matching criteria, the RAS group was divided into ACEi and ARB groups. Records of all groups were reviewed to determine the incidence of MC, 60 days after admission. We used Pearson's chi-squared test to compare the MC frequencies. Kaplan-Meier plot and log-rank test were used to compare time-to-event between groups. The strength of association was reported as Risk Ratios (RR) and 95% CI. A p-value &lt;0.05 was deemed significant. Results: Patients using RAS inhibitors had a higher risk of 60-day MC than those who did not (RR = 3.71, 95% CI = 1.61-8.58, p = 0.0017). The p-value of the log-rank test for the 60-day Kaplan-Meier analysis was 0.0006. There was no significant risk difference between ACEi and ARB groups (RR = 0.4, 95% CI = 0.12-1.27, p = 0.18). (Figure 1) Discussion: Our study showed a significant increased risk of 60-day MC in COVID-19 patients taking RAS inhibitors, with no difference between ACEi and ARBs. A plausible explanation is that the RAS inhibition leads to cardiomyocyte's ACE2 overexpression, thereby permitting SARS-CoV-2's cellular entry. This interpretation is limited due to the inherent bias associated with retrospective research and the paucity of additional evidence.
Abstract 13659: Automated Detection of Aortic Stenosis From Single-View 2-Dimensional Echocardiography Using a Semi-Supervised, Contrastive Learning Approach
Authors: Evangelos K Oikonomou, Gregory Holste, Bobak Mortazavi, Zhangyang Wang, Rohan Khera
Journal: Circulation (2022)

Introduction: Early diagnosis of aortic stenosis (AS) is critical for its timely management. However, despite emergence of hand-held echocardiography, the detection and grading of AS requires Doppler imaging, which is limited by both access and expertise. We developed a semi-supervised, contrastive learning approach to identify severe AS using limited labelled data of parasternal long axis (PLAX) videos from transthoracic echocardiography (TTE). Methods: We sampled TTE studies performed between 2015-2021 in a large health system. TTEs from 2015-2020 were used for training, with oversampling of AS for diagnostic enrichment (5311 studies, age 70±16 years, n=2601 [49%] women, 5029 unique patients). The testing set represented studies in 2021 without oversampling for AS (2040 studies, mean age 66±16 years, n=997 [49%] women, n=2034 unique patients). We performed self-supervised pretraining by selecting different PLAX videos from the same patient as positive samples for contrastive learning (multi-instance self-supervised learning) ( A ). The learned weights were used to initialize a 3D convolutional neural network to predict severe AS ( B ). Results: An ensemble model of three different weight initialization methods achieved an AUC of 0.97 (95% CI: 0.96-0.99) for severe AS detection, with 0.96 (95% CI: 0.83-0.97) specificity at 90% sensitivity. Among patients without severe AS, positive predictions were characterized by significantly higher peak aortic velocities compared to negative predictions, with no differences in LV function - a negative control ( C ). Saliency maps highlighted the aortic valve as most relevant to the final predictions ( D, i-v: positive; vi: negative predictions). Conclusions: We have developed a novel method to detect severe AS using single-view TTE videos without requiring Doppler data. Our findings have significant implications for point-of-care ultrasound screening as part of routine clinic visits and in low-resource settings.
Abstract 13367: APOE ε4 Carriage Associates With Improved Myocardial Performance in Older Age
Authors: Constantin-Cristian Topriceanu, Matthew Webber, Fiona Chan, James Moon, Nishi Chaturvedi, Alun Hughes, Jonathan Schott, Marcus Richards, Gabriella Captur
Journal: Circulation (2022)

Introduction: Although APOE ε 4 allele carriage confers a risk of coronary disease, its persistence in human populations might be explained by certain survival advantages (antagonistic pleiotropy) . Hypothesis: Combining data from two British cohorts– the 1946 National Survey of Health and Development (NSHD) and Southall and Brent Revised (SABRE)–we explored whether APOE ε 4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional echocardiography parameters in older age. Methods: Based on the presence of APOE ε 4, genotypes were divided into: APOE ε 4 (ε2ε4, ε3ε4, ε 4 ε 4) and non- APOE ε 4 carriers. Echocardiographic data included: LV ejection fraction, E/e’, systolic and diastolic posterior wall and interventricular septal thickness (LVPWT s/d , IVS s/d ), LV mass and the ratio of the LV stroke volume to the LV myocardial volume called myocardial contraction fraction (MCF). Generalized linear models explored associations between APOE ε 4 genotypes as exposures and echocardiographic biomarkers as outcomes. As APOE genotype is a genetic instrumental variable (unconfounded), Model 1 was unadjusted. Model 2 was adjusted for factors associated with the outcome (sex and socio-economic position) to yield more precise estimates; subsequent models were individually adjusted for mediators (body mass index, cardiovascular disease [CVD], high cholesterol and hypertension) to explore mechanistic pathways. Random-effects meta-analyses were performed across the cohorts. Results: 2596 participants were included. Compared to non- APOE ε 4 carriers, APOE ε 4 carriers had similar cardiac phenotypes in terms of EF, E/e’, LVPWT s/d , IVS s/d and LV mass but had a 4% higher MCF (95% confidence interval [CI]: 1–7%, p =0.016) which persisted in Model 2 (95% CI 1–7%, p =0.008) but was attenuated to 3% after adjustment for CVD, diabetes and hypertension (all 95% CI 0–6% all p &lt;0.070). Conclusions: APOE ε 4 carriage associates with improved myocardial performance in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to APOE ε4 carriage that might collectively explain its persistence in humans.
Abstract 13581: Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Cancer Therapy-Related Cardiac Dysfunction
Authors: Julia Kar, A'Mere Bryant, Anam Chouhdry, Michael Cohen, Cherie Revere, Samuel McQuiston, Christopher Malozzi
Journal: Circulation (2022)

Introduction: This prospective study aimed to determine if MRI-imaging and Artificial Intelligence (AI)-based computation of global longitudinal strain (GLS) in the left ventricle (LV) is an early predictor of cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients. Hypothesis: To show with risk analysis that GLS is an independent prognosticator of CTRCD when compared to LV ejection fraction (LVEF) with the patient cohort administered antineoplastic chemotherapy treatment. Methods: Motion-encoded data with Displacement Encoding with Stimulated Echoes (DENSE) MRI were acquired on 32 breast cancer patients at baseline and 3- and 6-months follow-ups after chemotherapy. Automated image segmentation for chamber quantification and phase-unwrapping in the LV occurred with two DeepLabV3+ fully convolutional networks (FCNs), and 3D strains computed with the meshfree Radial Point Interpolation Method. CTRCD (including adverse cardiac events and cardiotoxicity) risk analyses with the measured clinical, chamber quantification, and strain parameters were conducted with univariable and bivariable Cox proportional hazard (PH) regressions. Results: GLS worsened from baseline to the 3- and 6-months follow-ups (-19.1 ± 2.1% vs. -16.0 ± 3.1% vs. -16.1 ± 2.9%, P&lt;0.001) (Fig. 1). With univariable Cox regression, the 3-months follow-up GLS was independently associated as an agonist (hazard ratio [HR]-per-SD: 2.1; 95% CI: 1.4-3.1, P&lt;0.001) and LVEF as protector (HR-per-SD: 0.8; 95% CI: 0.7-0.9, P&lt;0.001) for CTRCD occurrence. In bivariable regression, GLS (HR-per-SD: 2.0; 95% CI: 1.2-3.4, P=0.01) was an independent predictor of CTRCD regardless of LVEF (HR-per-SD: 1.0; 95% CI: 0.9-1.2, P=0.9) as covariate. Conclusions: The end-point risk analyses show that LV GLS is an early CTRCD predictor independent of LVEF in breast cancer patients treated with antineoplastic chemotherapy. GLS should be a standard metric for the clinical diagnosis of CTRCD.
Abstract 14034: 30-day Readmission Rates of Cardiogenic Shock: A Nationwide Analysis of Inpatient Demographics and Clinical Outcomes
Authors: Richard Amoateng, Ibrahim Ahmed, Matthew Lander
Journal: Circulation (2022)

Introduction Cardiogenic shock (CS) is a common medical emergency that causes significant morbidity and mortality. Our aim was to characterize patient demographics and analyze the factors that increase the likelihood for CS readmissions. Methods This was a retrospective cohort study using the 2019 Nationwide Readmissions Database (NRD) database to identify admissions in adults with principal diagnosis of CS. Results The index CS admission cohort was 62.2% males, mean age 66.9 years. Of 146,254 index admissions with CS, 19,238 (20.4%) were readmitted. 30-day mortality rate (MR) of index admission was 35.4%, with a MR of 9.7% in those readmitted. The most common cause for readmissions was acute heart failure (26.7%). Patients with the lowest median household income, Medicare, and Medicaid insurance were more likely to be readmitted (1.10 OR 95% CI 1.04 -1.16, p &lt;0.01, 1.17 OR 95% CI 1.11-1.24, p &lt;0.001 and 1.27 OR 95% CI 1.12-1.86, p &lt;0.001 respectively). Meanwhile, being in the highest median household income quartile (&gt;75 th ) or having private insurance were protective against readmission. Acute MI patients were less likely to be readmitted (0.83 OR 95% CI 0.79 -0.87, p &lt;0.001). Diastolic HF and CHF were associated with increased odds of readmission when adjusted for other comorbidities, age, and gender (2.52 OR 95% CI 1.09-5.83, p&lt;0.031 and 2.15 OR 95% CI 1.01-4.57, p&lt;0.046 respectively). Conclusion Readmission after CS is common, with high mortality. Risk factors for readmission include lower household income and Medicare/Medicaid insurance, and those that leave AMA after index cardiogenic shock admission have increased odds of readmission. Conversely, those with the highest median household income and with private insurance had a significantly lower rate of readmission. Additional research is needed to elucidate the contributing factors for this stark difference.
Abstract 13023: Exercise Training Potentiates Diuretic Benefits on Mechanism of Arterial Pressure Control in Hypertensive Postmenopausal Rats: Role of Inflammatory and Redox Balance
Authors: Maycon Ferreira, Danielle d Dias, Gabriel d Silva, Michel P Silva, Amanda A Araujo, Camila P Santos, Marina Dutra, Nathalia Bernardes, Maria Claudia Irigoyen, katia de angelis
Journal: Circulation (2022)

Introduction: Thiazide diuretic is a classic drug used to treat elevated arterial pressure (AP). However, their neuroinflammatory effects are limited when compared with other therapies. Objective: To compare the effect of hydrochlorothiazide (HCTZ) alone or combined with concurrent exercise training (aerobic+resistance, CET) on mechanisms of AP control and on inflammatory and redox balance in hypertensive postmenopausal rats. Methods: Female spontaneously hypertensive rats were distributed into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with HCTZ (OSH), trained (OT) and trained treated with HCTZ (OTH). HCTZ treatment (30 mg/kg) and CET (40-60% maximal capacity, 3 days/wk) were conducted for 8wks. AP was directly recorded at rest and after vasopressor system blockade (vasopressin antagonist, losartan and hexamethonium). Inflammation and oxidative stress were evaluated in cardiac tissue. Results: Trained groups presented higher exercise tests performance. Systolic (OT:178±18 and OTH:178±17 vs. OS:205±15) and mean AP (mmHg) (OTH:153±17 vs. OS:176±16) were reduced in trained groups. CET promoted an increase in both bradycardic and tachycardic responses of baroreflex sensitivity and a reduction in AP variability indexes in relation to OS group. After sympathetic blockade, AP (mmHg) reduction was higher in OS group (-75.7±19.2 vs. S:-53.2±12.6 and OTH:-49.8±12.4). In addition, IL-10 (OTH vs. OS and OSH) and IL-10/TNF-alpha ratio (OTH vs. S, OS, OSH and OT) were higher in OTH group. OS group showed increased NAPDHoxidase and reduced catalase (vs. S); however, these changes were not observed in OTH group. Negative correlation was observed between sympathetic vascular modulation and IL/TNF-alpha ratio (p&lt;0.001, r:-0.6). Conclusions: We concluded that CET alone or combined with HCTZ are more efficient approaches than HCTZ to reduce AP and improve AP control of circulation. Specifically, the combination HCTZ plus CET induces additional positive adaptations on physical, autonomic, inflammatory and redox balance. These results highlight the key role of exercise in the management of HTN, probably impacting on the quality of life and reducing the residual risk in post menopause. Grants: FAPESP (2019/06277-0).
Abstract 13962: Anemia Correction Improves Mortality and Other Outcomes in Patients With Incident Atrial Fibrillation: A Nationwide Cohort Study
Authors: Jee Hyuk Byun, Ha Jeong Lim, Pil-sung Yang, Jung-Hoon Sung, BOYOUNG JOUNG
Journal: Circulation (2022)

Background: Emerging evidence has suggested that anemia in patients with atrial fibrillation (AF) may lead to poor outcomes. We investigated the association of anemia after AF diagnosis with mortality and cardiovascular (CV) events. Methods: Using the database of Korean National Health Insurance Service and health examination, a total of 102,801 patients newly diagnosed with AF (2005-2015) were categorized into four groups according to the status of anemia before and after AF diagnosis. The primary outcomes were all-cause mortality and composite of CV death, ischemic stroke, heart failure hospitalization, or acute myocardial infarction. Results: The median follow-up duration was 5.3 years. Among AF patients with anticoagulation, the non-anemia to anemia and consistent anemia groups were associated with a higher risk of mortality (hazard ratio [95% CI]: 1.56 [1.34-1.80] and 1.59 [1.30-1.95]) and CV composite outcome (1.30 [1.15-1.47] and 1.28 [1.09-1.51]) compared to the consistent non-anemia group, respectively. Correction of anemia after diagnosis of AF (anemia to non-anemia group, HR [95%CI]: 1.38 [1.13-1.69]) showed a lower risk of mortality compared to the patients with persistent uncorrected anemia (consistent anemia group, 1.59 [1.30-1.95]). These results were consistently observed in AF patients without anticoagulation. Conclusions: Anemia was associated with an increased risk of mortality and CV outcomes in patients with newly diagnosed AF. Anemia correction after AF diagnosis could reduce the risk of subsequent CV events and mortality. Correction of anemia should be encouraged as part of a comprehensive approach to AF management to improve outcomes.